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genetics
Extracellular
signal = ;
Inactiv= e
Ras= = ;
GDP= = ;
Active<= /b>
Ras= = ;
GTP= = ;
=
<= ![endif]>
=
=
GTP= = ;
GDP= = ;
1.
Extrace= llular
signal influences
the sta= te of the Ras protein
2. <= /div>
Ras pro= tein is activated by phosphorylation of bound GDP and inactivated dephosphorylation of bound&= nbsp; GTP= = ;
<= span style=3D'mso-special-format:lastCR;display:none'>
P = ;
3. <= /div>
Active = Ras protein = transducessigsignal to the = nucleus  
GTP= = ;
=
=
=
=
4. <= /div>
This si= gnal regulates transcription <= /span>= of genes = involved in = cell division
TRANSCRIPTION
=
=
Cell di= vision = ;
5. <= /div>
Cell di= vision occures in a controlled fashion
=
Ras = ;
Protooncogene c-ras= task 11, page 186-187
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Extracellular
sign= al = ;
Inactive
Ras = ;
GDP
=
Active
Ras = ;
GTP
=
<= span style=3D'mso-special-format:lastCR;display:none'>
=
GTP
GDP
Ras protein is= active wi= thout any extracellular signaling ® there is no co= nversion GTP= t= o GDP<= span style=3D'font-size:133%;text-decoration:none;color:red;mso-special-format:= lastCR; display:none'>
Ras protein = remains acti= ve
GTP
=
=
=
 
The signa= l continuously= induces the<= /b> transcription of = genes involv= ed in cell cycle <= /b>regulation
TRANSC<= span style=3D'font-size:92%;text-decoration:none'>RIPTION = ;
=
=
Ce= ll division is uncontrolled
Ras
=
Point mutation – substituti= on T®G (= see genetic code, page 111)
Protooncogene c-ras= task 11, page 186-187
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=
Protooncogene c-ras
Commentary - protooncogene c-ras
G p= rotein ® GT= P-binding protein with signal <= /span>= transmitting function
<= span style=3D'font-size:56%'>Activated after binding growth factor to its receptor
Activation of receptor ® exchange of associated GDP = to GTP
GTP trigg= ers a short time-limited Ras signaling ability
<= span style=3D'font-size:56%'>Signaling pathway continues via MAP<= /span>-kinases
In the nucleus ® activation of transcription factors (e.g. product of c-myc)
Result:
R= 26;c-ras is inactivated af= ter short time by conversion = of = GTP to GDP =
= 226;     Several mutatio= ns in c-ras can remove the time = limit of the cell-st= imulated signal (hydrolys= is of GTP to GDP) and uncontrolled cell division leads to tumor devel= opment
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Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Tumor genetics
=
Tumor suppressor genes
= 226;NORMAL GENES – CELL CYCLE REGULATION  ® PREVENTION OF NEOPLASIA
MUTATION ® loss of gene f= unction
= 226;MUTATION  RECESIVE AT THE CELLULAR LEVEL (loss of function of both alleles)
AUTOSOMAL DOMINANT INHERITANCE = ;
HEREDITARY PREDISPOS= ITION ® GERMINAL MUTATION
(AT THE LEVEL OF = WHOLE ORGANISM)
•<= /span>Sporadic incidenc= e of tumor: two somatic mutations <= /b>® risk =3D frequency neoplasia in population=
<= span style=3D'font-size:63%;color:#CC3300'>Familial incidence: 1. germline mutation, 2. somatic mutation=
predisposition, early childhood, multifocal or bilateral incidence, several memmbers of fam= ily affected
<= span style=3D'font-size:63%'>tumor initiation - requires two steps (Knudson – two-= hit hypothesis) <= /b>
loss of heterozygosity in tumor cells (LOH) – e.g. linkage analysis Rb1 gene with gen<= /b>e coding enzyme esterase D (ma= rker)
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Tumor-suppressor genes – cause of loss of function
<= span style=3D'font-size:75%'>Deletion – could be found in different locations of a gene
<= span style=3D'font-size:75%'>Mitotic nondisjunction
<= span style=3D'font-size:75%'>Mitotic recombination
Uniparental disomy (both chromosomes  originate from  the same parent)
<= span style=3D'font-size:75%'>Point mutation
<= span style=3D'font-size:75%'>Protein inactivation (interaction with viral antigene)
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Tumor localisation
Gene
Chromoso= me
Gene act= ivity
eye (retinoblastoma), bone, breast, lung, urinary bladder, = prostate
Rb
13q14
Cell cycle regulation=
Kidney and other organs (WAGR syndrom)
WT1/W= T2
11p13
Cell cycle regulation=
Different types of tumors (aprox. 50% tumors – mutation of TP53)
TP53<= /i>
17p13
Regulati= on of cell cycle, transcriptional factor
colon (familial adenomatosis coli), stomach, non-inher= ited colorectal carcinomas=
APC
5q21
Regulati= on of β-= catenin l= evel, cell proliferation and adhesion
breast, ovary, prostate, larynx, digestive tract, pancreas
BRCA1=
BRCA2=
17p21 &#= 13;
13q12-q1= 3
Repair of double-stranded DNA breaks
Tumor suppressor genes – examples
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Tumor genetics
Tumor suppressor gene Rb1 (the most frequent mutation - microdeletion)
RECESIVE MUTATION
FIRST MUTATION – GERMLINE =
SECOND SOMATIC
Two-hit hypothesis
(Knudson)
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=
Tumor supressor gene RB1
= Reti= noblastoma ® tumors originate <= /span>= from the retina cells
Tumor of eye - in infancy or early childhood
1 / 15000-18000 live birth
Non-hereditary form – 60% (one eye), = two somatic mutations 
Familial incidence – 40% (bilateral, multifocal)
Germline mutation, transmited as an autosomal dominant trait
M= utation - both genes
<= /div>
a shimmer ou= t of the affected eye
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=
Rb1 gene – ubiquitously expressed
Cell cycle regulation
= gene product – nuclear phosphoprotein (pRb - 100kD)
phosphorylation / dephosphorylation (serine and threonine residues)
dephosphorylation of protein Rb – active form ® inactivation of transcriptional fact= or E2F
® cell cycle block in G1
phosphorylated pRb (inactive) ® E2F released from complex pRb/E2F
transition fom G1 to S phase of interphase

TU= MOR SUPPRESSOR GEN <= b>Rb1

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Tumor suppressor genes and cell cycle
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Content-Location: file:///C:/A4243E38/onko_en08_soubory/slide0142.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Tumor genetics
Tumor suppressor gene Rb1 – page 182-183
fragment size (kb) = ;
patient=   with bilateral
retinob= lastoma = ;
patient with unilateral
retinob= lastoma = ;
normal
fibroblasts
 fibroblasts
 fibroblasts
 tumour
 tumour
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7,5
5,3
9,8
6,2
 restriction map: sizes and order of HindIII restriction fragments in the retinoblastoma gene
9.8
7.5
6.2
5.3
<= /span>
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7,5<= /b>
5,3<= /b>
9,8<= /b>
6,2<= /b>
7,5<= /b>
5,3<= /b>
9,8<= /b>
6,2<= /b>
7,5<= /b>
5,3<= /b>
9,8<= /b>
6,2<= /b>
6,2<= /b>
Germline mutati= on
6,2<= /b>
Somatic mutation=
=
7,5
5,3
7,5
Two different s= omatic mutati= ons
FIBROBLASTS<= /b>
RETINOBLASTO= MA
fragment size (kb) = ;
patient=   with bilateral
retinobl= astoma = ;
patient with unilateral
retinob= lastoma = ;
normal
fibroblasts
 fibroblasts
 fibroblasts
 tumour
 tumour
=
=
=
=
=
=
=
=
=
7,5
5,3
9,8
6,2
 restriction map: sizes and order of HindIII restriction fragments in the retinoblastoma gene
9.87.5 =
6.2
5.3
<= /span>
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<= span style=3D'font-size:63%'>Product= s BRCA genes form complex with products of several genes <= /div>
<= span style=3D'font-size:63%'>Cell cy= cle regulation
<= span style=3D'font-size:63%'>Repair – doublestrand breaks of DNA
Inherited mutation of BRCA1 – familial incidence breast cancer and/or cancer of ovary
Germline mutation of BRCA2 gene – association with cancer of breast (both female and male), prostate and pancreas
<= span style=3D'font-size:63%'>proteine BRCA1 and BRCA2 ®= cooperation with protein RAD51
<= span style=3D'font-size:63%;visibility:hidden'>
= 226;Mutation of BRCA1 / BRCA2 gene – trunc= ated protein (loss of function) =
Tumor suppressor genes BRCA1, BRCA2 – page 178=
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Familial incidence of tumors associated with BRCA2
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Breast cancer=
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Breast cancer
Pancreatic cancer
Prostate cancer
Stomach and prostate cancer
Breast cancer
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Sporadic and familial incidence of breast cancer - females
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charset="us-ascii" Tumor genetics
     Alleles        = ;  Mother      Father       Daughter<= /span>     Daughter= ‘s breast cancer <= /span>
        = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp; 
+
-
2
1
Linkage analysis:<= /span> marker gene <= /b>(allele 1 and 2) - gene BRCA1 - = page 179
BRCA1+/+
BRCA1+
Deletion, mitotic nondisjunct= ion ..= .
BRCA1-
BRCA1-
BRCA1+
BRCA1-
BRCA1-, e.g. substitution
Examined cells of mother, father and daughter: fibroblasts or leukocytes
Loss of h= eterozygosity (LOH) in breast cancer cells
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Familial incidence of breast and ovary cancer= page 181 (pedigree study)
=
=
Ov= = ;
J
A
L = ;
B
C
G = ;
G
E
E = ;
H
F
G = ;
=
Ov 44<= /b> = ;
J
A
L = ;
G
E
E = ;
F
B
K = ;
H
D
F = ;
I= = ;
II = ;
1 = ;
2 = ;
1 = ;
2 = ;
70
B
C
G = ;
H
F
G = ;
D
B
G = ;
H
C
H = ;
3 = ;
4 = ;
75 = ;
J
A
L = ;
H
F
G = ;
F
E
K = ;
F
E
I = ;
5 = ;
6 = ;
50 = ;
B
C
G = ;
H
C
H = ;
4 = ;
5 = ;
B
C
G = ;
H
C
H = ;
III = ;
=
43 = ;
F
B
K = ;
1 = ;
2 = ;
H
D
F = ;
3 = ;
F
B
K = ;
G
E
E = ;
47 = ;
Br 42&= #13;
Ov 46<= /b> = ;
H
F
G = ;
F
E
K = ;
6 = ;
7 = ;
J
A
L = ;
F
E
K = ;
8 = ;
J
A
L = ;
F
E
K = ;
Br 39&= #13;
Ov 50<= /b> = ;
G
E
E = ;
G
E
E = ;
F
E
F = ;
F
E
K = ;
9 = ;
Br 31&= #13;
J
A
L = ;
F
E
K = ;
2 = ;
J
A
L = ;
F
E
F = ;
3 = ;
F
E
K = ;
F
E
F = ;
 30
 28
IV = ;
1 = ;
=
=
=
=
Lifelong ris= k:
daughter= IV/2: 80% ( <= span lang=3DEN-US style=3D'font-size:150%;text-decoration:none'>germline = mutation) <= /div>
daughter= IV/3: aprox. 10% (risk = of sporadic incidence)
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=
Mutator genes – mismatch repair (MMR)=
= 226; As= sociation with  HNPCC (Hereditary Nonpolyposis Colon Cancer)
hMSH2, hMLH1, hPMS1, hPMS2, hMSH6, <= span style=3D'position:absolute;top:32.5%;left:6.92%;width:52.99%;height:4.25%'= >hMSH3
genome stability
mismatch r= epair (replication errors)
microsatel= lite loci (e.g. CAn) instability&#= 13;
<= span style=3D'font-size:63%'>increased mutation frequency 100 –1000x
<= span style=3D'font-size:63%'>recessive character  of mutation in MMR genes
<= span style=3D'font-size:63%'>autosomal dominant heritability HNPCC
<= span style=3D'font-size:63%'>Lynch synd= rome I – colon and rectal cancer
Lynch syndrome II - cancer of colon and rectum, 30% - tumor  endometrium, stomach, pancreas, urinary tract
=
3Dpeople
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= =3D9711gen7 =
Mismatch repair -= hMSH2
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Nonrandom (primary)
Philadel= phia chromosome (Ph1)
Translocation – Burkitt lymphoma =
Amplification, double-minutes
Random (secondary)
random chromosomal aberrations (deletions, translocations, dicentric chromosome, ring chromosome, isochromosome ….)
heteroploidy, for example pseudodiploidy
Nonrandom chromosomal aberrations i= n tumor cells
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Nonrandom chromosomal aberration
  Burkitt´s lymphoma
Translocation of protoonkogene c-myc t(8;14), or rarely t(8,22), t(2,8)
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Nonrandom chromosomal aberration
Chronic myeloid leukemia (CML)
Philadelphia chromosome (Ph) <= /span>
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Philadelphia (Ph) chromos= ome - reciprocal translocation - chromosome 9 and 22 - { t(9;22)(q34;= q11) }
Cytogenetic prognostic marker - 90% CML =
Cytogenetic marker - 5 -20% acute lymphocytic leukemia (ALL) 
Translocation = ® fusion genes  BCR-ABL, break in BCR ("breakpoint cluster region") gene (chromosome 22 and ABL protooncogene  chromosom 9 )
Chimeric proteine 210 kD - oncoprotein
Chronic myeloid leukemia (CML)
Philadelphia chromosome (Ph)
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Nonrandom chromosomal aberra= tion
Amplification - protooncogene N-myc=
Amplification of DNA sequence
A) homogenously stained regions (HSR)
B) double minutes
diagnostic and prognostic marker
family of myc protooncogenes (virus of chicken myeloblastosis) cell cycl= e regulation
•<= /span>N-myc – neuroblastoma
L-myc – small cell lung carcinoma
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SIJcSIMUioAAADs= ------=_NextPart_01C95CB4.1262E6F0 Content-Location: file:///C:/A4243E38/onko_en08_soubory/slide0088.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Tumor genetics
=
FISH methods<= /span>
= 226;FISH = diagnostic tool of clasical cytogenetics combined with molecular genetic appro= ach
= 226;Based= on hybridization of single stranded DNA probe with single stranded seque= nce of studied DNA in situ (based on the complementarity rule)
Exami= nation of chromosomes in mitotis or interphase
DNA prob= e is labeled with fluorochrome (eg. Texas Red, FITC, etc.)
= 226;Types of DNA probes – centromerical, locus-specific, painting of chromosomes =
= 226;
Centromeric probes: a-satelli= te sequences of repetitive DNA present in centrome= ric regions ® detection of abnormal chromosome number
    
= 226; Locus-specific probes: hybridization with specific loci on chromosom= es ® detection of structural aberrations = (microde= letion, translocations…)
= 226; Painting of whole chromosomes: mix of chromosome-specific DNA fragments enables to distinguish diffe= rent chromosomes, but cannot be used for interphase chromosomes <= /b>
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Locus-specific p= robe – breast cancer cell in interphase
Protooncogen<= b>e Her-2/neu<= /b><= b> <= b>
 epidermal gr= owth factor r= eceptor  (tyrosine kinase activity)<= span style=3D'font-size:167%;text-decoration:none;display:none'>
Prognostic and diagnostic marker <= /span> breast cancer,= urinary bladder ….<= /b>        = ;            &n= bsp;            = ;            &n= bsp;         
Centromeregreen signa= l -2x
Her-2/neu – red signa= l – 2x
Normal cell
Centromere= green signa= l -2x (two homologous = chromosomes)
= Her-2/neu – red signa= l – amplific= ation of gene (6x); = second chromosome 1x (no mutation)
Tumor cell
Determine w= hich picture represents situation in tumor cell: =
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Small-cell carcinoma of lung
•<= /span>FISH method<= /span> - „smear“,  single signals are undete= ctable
Multiple copies (amplification ) of protoonco= gene= L-myc - <= b>non-random chromosom<= b>al aber<= b>ra<= b>tion<= b>
Bad prognosi= s
Determine which type of chromosomal aberr= ation represents the picture:<= /div>
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Multicolor painting probe – karyotype of lung tumor
hyperdiploidic  number of chromosomes + random structural aberrations
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Content-Location: file:///C:/A4243E38/onko_en08_soubory/slide0155.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Tumor genetics
=
=
Chromosomal aberrations in brea= st cancer cells
 
Chromosom<= b>es <= b>in breast cancer cells - multiple <= b>random aberrations
Breast cancer cells<= /b> – amplification of protooncogen<= b>e Her-2/neu
Amplification in majority of cancer<= /span> <= b>cells (many s= ignals ®= &#= 8220;smear&#= 8221;<= b>
Non-random (primary) chromosomal <= b>aberration
Karyotype ® <= b>diagnostic marker, associated with prognosis a= nd choice of therapy
Detection of Her-2/neu us= ing FISH
Determine wh= ich picture represents random and which one non-random chromosomal aberr= ations.
Multicolor FISH
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charset="us-ascii" Tumor genetics
Comparative genome hybridizatio= n (CGH)
Comparative genome hybridization (CGH) – molecular cytogenetic method
Identification of multiple chromosomal non-balanced aberrations in tumor cells, balanced aberrations are not detected using CGH
Pathological event must be found at least in 50% cells
Genomic DNA from normal and tumor tissue ® simultaneous in situ hybridization with methaphas= e chromosomes of normal (healthy) cell
Detection : (i) green fluorescent labeled probe<= /b> = DNA of tumor=
        = ;            (ii) red fluorescent labeled probe - DNA of normal tissue (control      = sample of DN= A)
Ratio of gre= en to red fluo= rescent= signal intensity gives the ratio of difference between = DNA isolated fro= m normal and tumor cells
CGH analysis require<= /span>s an equipment <= span style=3D'font-size:167%;text-decoration:none'>for quantitative analysis of fluorescent signal
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3D"cgh_abn" <= ![endif]>
Comparative genomic hybridizati= on (CGH)
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g_bgSound ) { idx=3Dg_bgSound.indexOf(","); pptSound.src=3Dg_bgSound.substr( 0, idx ); pptSound.loop=3D -(parseInt(g_bgSound.substr(idx+1))); } SlideObj.filters.revealtrans.Apply() } SlideObj.style.visibility=3D"visible" if( fTrans ) SlideObj.filters.revealtrans.Play() } function MakeNotesVis() { if( !IsNts() ) return false SlideObj.style.display=3D"none" nObj =3D document.all.item("NotesObj") parent.SetHasNts(0) if( nObj ) { nObj.style.display=3D"" parent.SetHasNts(1) } return 1 } function ChkAutoAdv() { if(SldHasTrans()) SlideObj.onfilterchange=3DAutoAdv else AutoAdv() } function AutoAdv() { if(!IsWin("PPTSld") || !gUseSldTimings )return var sld=3DGetCurSld() if( (sld.mAdvDelay>0) && !parent.IsFramesMode() ) setTimeout("parent.GoToNextSld()",sld.mAdvDelay) } function GetObj(id) { if(g_supportsPPTHTML) return document.all(id); else return document.getElementById(id); } function SldHasTrans() { return SlideObj.style.filter !=3D ""; } function GetSldId() { return sId=3Dlocation.href.substring(location.href.la= stIndexOf('/')+1) } function HideMenu() { if( frames["PPTSld"] && PPTSld.document.all.item("ctx= tmenu") && PPTSld.ctxtmenu.style.display!=3D"none" ) { PPTSld.ctxtmenu.styl= e.display=3D'none'; return true } return false } function IsWin( name ) { return window.name =3D=3D name } function IsNts() { return IsWin("PPTNts") } function IsSldOrNts() { return( IsWin("PPTSld")||IsWin("PPTNts") ) } function SupportsPPTAnimation() { return( navigator.platform =3D=3D "Win32"= && navigator.appVersion.indexOf("Windows")>0 ) } function SupportsPPTHTML() { var appVer=3Dnavigator.appVersion, msie=3DappVer.indexOf("MSIE "), ver=3D0 if( msie >=3D 0 ) ver=3DparseFloat( appVer.substring( msie+5, appVer.indexOf(";",msie) ) ) else ver=3DparseInt(appVer) return( ver >=3D 4 && msie >=3D 0 ) } function _RSW() { if( !g_supportsPPTHTML || IsNts() || ( !g_scaleInFrame && (!IsWin("PPTSld") || !parent.IsFullScrMode()) ) ) return var padding=3D0; if( IsWin("PPTSld") && parent.IsFramesMode() ) padding=3D6 cltWidth=3Ddocument.body.clientWidth-padding cltHeight=3Ddocument.body.clientHeight-padding factor=3D(1.0*cltWidth)/g_origW if( cltHeight < g_origH*factor ) factor=3D(1.0*cltHeight)/g_origH newSize =3D g_origSz * factor if( newSize < 1 ) newSize=3D1 s=3DSlideObj.style s.fontSize=3DnewSize+"px" s.posWidth=3Dg_origW*factor s.posHeight=3Dg_origH*factor s.posLeft=3D(cltWidth-s.posWidth+padding)/2 s.posTop=3D(cltHeight-s.posHeight+padding)/2 if( g_scaleHyperlinks ) ScaleHyperlinks( factor ) } function _InitAnimations() { animRuntimeInstalled =3D ''+document.body.localTime !=3D 'undefined'; isFullScreen =3D (window.name =3D=3D "PPTSld") && !parent.IsFramesMode(); g_animUseRuntime =3D g_showAnimation && animRuntimeInstalled && !(isFullSc= reen && parent.IsSldVisited()); if( g_animUseRuntime ) { collSeq =3D document.all.tags("seq"); if( collSeq !=3D null ) { for(ii=3D0;ii numSlds ) gSldJumpIdx =3D numSlds; if ( gSldJumpIdx >=3D 0 ) { if ( gSldJumpIdx =3D=3D 0 ) gSldJumpIdx =3D 1; var jumpTo =3D parseInt(gSldJumpIdx); gSldJump =3D 0; gSldJumpIdx =3D ""; win.GoToSld( parent.GetSldList().mList[jumpTo-1].mSldHref ) } } } function _KDH() { if( event.keyCode =3D=3D 8 ) { event.returnValue =3D 0; parent.GoToPrevSld(); } } function DocumentOnClick() { if( IsNts() || parent.HideMenu() ) return; if( ( g_allowAdvOnClick && (window.name=3D=3D"PPTSld") && !parent.IsFrames= Mode() ) || (event && event.keyCode=3D=3D32) ) { if( g_animUseRuntime && g_animMainSequence && g_animMainSequence.cangonex= t ) return; parent.GoToNextSld(); } } var g_supportsPPTHTML =3D SupportsPPTHTML(), g_scaleInFrame =3D 1, gId=3D""= , g_bgSound=3D"", g_scaleHyperlinks =3D false, g_allowAdvOnClick =3D 1, g_showInBrowser = =3D 0, gLoopCont =3D 0, gUseSldTimings =3D 1; var g_showAnimation =3D g_supportsPPTHTML && SupportsPPTAnimation() && ( (w= indow.name=3D=3D"PPTSld" && !parent.IsFramesMode()) || g_showInBrowser );va= r g_animManager =3D null; var g_animUseRuntime =3D false; var g_animItemsToHide, g_animInteractiveItems, g_animSlideTime; var g_animMainSequence =3D null; var ENDSHOW_MESG=3D"Konec prezentace, klepnutím ukončíte= předvádění.", SCREEN_MODE=3D"Frames", gIsEndShow= =3D0, NUM_VIS_SLDS=3D32, SCRIPT_HREF=3D"script.js", FULLSCR_HREF=3D"fullscr= een.htm"; var gCurSld =3D gPrevSld =3D 1, g_offset =3D 0, gNtsOpen =3D gHasNts =3D gO= tlTxtExp =3D 0, gHasNarration =3D 0, gOtlOpen =3D true window.gPPTHTML=3DSupportsPPTHTML() var gMainDoc=3Dnew Array(new hrefList("slide0136.htm",1,-1,1),new hrefList(= "slide0132.htm",1,-1,1),new hrefList("slide0139.htm",1,-1,1),new hrefList("= slide0140.htm",1,-1,1),new hrefList("slide0150.htm",1,-1,1),new hrefList("s= lide0138.htm",1,-1,1),new hrefList("slide0159.htm",1,-1,1),new hrefList("sl= ide0111.htm",1,-1,1),new hrefList("slide0133.htm",1,-1,1),new hrefList("sli= de0134.htm",1,-1,1),new hrefList("slide0135.htm",1,-1,1),new hrefList("slid= e0142.htm",1,-1,1),new hrefList("slide0144.htm",1,-1,1),new hrefList("slide= 0151.htm",1,-1,1),new hrefList("slide0146.htm",1,-1,1),new hrefList("slide0= 147.htm",1,-1,1),new hrefList("slide0148.htm",1,-1,1),new hrefList("slide01= 49.htm",1,-1,1),new hrefList("slide0125.htm",1,-1,1),new hrefList("slide012= 7.htm",1,-1,1),new hrefList("slide0025.htm",1,-1,1),new hrefList("slide0096= .htm",1,-1,1),new hrefList("slide0098.htm",1,-1,1),new hrefList("slide0099.= htm",1,-1,1),new hrefList("slide0100.htm",1,-1,1),new hrefList("slide0088.h= tm",1,-1,1),new hrefList("slide0152.htm",1,-1,1),new hrefList("slide0153.ht= m",1,-1,1),new hrefList("slide0160.htm",1,-1,1),new hrefList("slide0155.htm= ",1,-1,1),new hrefList("slide0156.htm",1,-1,1),new hrefList("slide0157.htm"= ,1,-1,1)); function FullScrInit() { g_allowAdvOnClick =3D GetCurSld().mAdvOnClk document.body.style.backgroundColor=3D"black" document.oncontextmenu=3Dparent._CM; document.onkeydown =3D _KDH; document.ondragstart=3DCancel document.onselectstart=3DCancel self.focus() } function Redirect( frmId ) { var str=3Ddocument.location.hash,idx=3Dstr.indexOf('#'), sId=3DGetSldId() if(idx>=3D0) str=3Dstr.substr(1); if( window.name !=3D frmId && ( sId !=3D str) ) { obj =3D GetObj("Main-File") window.location.href=3Dobj.href+"#"+sId return 1 } return 0 } var MHTMLPrefix =3D CalculateMHTMLPrefix(); function CalculateMHTMLPrefix() { if ( document.location.protocol =3D=3D 'mhtml:') { href=3Dnew String(document.location.href) Start=3Dhref.indexOf('!')+1 End=3Dhref.lastIndexOf('/')+1 if (End < Start) return href.substring(0, Start) else return href.substring(0, End) } return ''; } function GetTags(base,tag) { if(g_supportsPPTHTML) return base.all.tags(tag); else return base.getElementsByTagName(tag); } function UpdNtsPane(){ if(frames["PPTNts"]) PPTNts.location.replace( MHTMLP= refix+GetHrefObj( gCurSld ).mNtsHref ) } function UpdNavPane( sldIndex ){ if(gNavLoaded) PPTNav.UpdNav() } function UpdOtNavPane(){ if(gOtlNavLoaded) PPTOtlNav.UpdOtlNav() } function UpdOtlPane(){ if(gOtlLoaded) PPTOtl.UpdOtl() } function SetHasNts( fVal ) { if( gHasNts !=3D fVal ) { gHasNts=3DfVal UpdNavPane() } } function ToggleOtlText() { gOtlTxtExp=3D!gOtlTxtExp UpdOtlPane() } function ClearMedia() { if (PPTSld.pptSound) PPTSld.pptSound.loop =3D 0; } function FullScreen() { if ( PPTSld.g_animUseRuntime ) PPTSld.document.body.pause(); ClearMedia(); var href =3D ( document.location.protocol =3D=3D 'mhtml:') ? FULLSCR_HREF = : FULLSCR_HREF+"#"+GetHrefObj(gCurSld).mSldHref; if(PPTNav.event.ctrlKey) { var w =3D (window.screen.availWidth * 1.0) / 2.0 var h =3D w * (PPTSld.g_origH * 1.0) / PPTSld.g_origW win =3D window.open( MHTMLPrefix+href,null,"toolbar=3D0,resizable=3D1,top= =3D0,left=3D0," + "width=3D"+ w + ",height=3D" + h ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } else { win =3D window.open( MHTMLPrefix+href,null,"fullscreen=3Dyes" ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } } function ToggleVNarration() { rObj=3DPPTSld.document.all("NSPlay") if( rObj && !PPTSld.g_animUseRuntime ) { if( (rObj.playState =3D=3D 1)||(rObj.playState =3D=3D 0) ) rObj.Play() else if( rObj.playState =3D=3D 2 ) rObj.Pause() else return; } else if( PPTSld.g_animUseRuntime ) { narObj =3D PPTSld.document.all("narrationID") if( narObj ) narObj.togglePause() } } function GetCurSldNum() { obj=3DGetHrefObj(gCurSld) if( obj.mOrigVis =3D=3D 1 ) return obj.mSldIdx else return gCurSld } function GetNumSlds() { if( GetHrefObj(gCurSld).mOrigVis =3D=3D 1 ) return GetSldList().mNumVisSlds; else return GetSldList().mList.length } function GetSldNum( href ) { for(ii=3D0; ii 1 ) PopSldList(); else if( !IsFramesMode() ) { if( gLoopCont ) GoToFirst() else EndShow() } } function GoToPrevSld() { ii=3DgCurSld-1 if( ii > 0 ) { obj=3DGetHrefObj(ii) while ( obj && ( obj.mVis =3D=3D 0 ) && ( ii>0 ) ) obj=3DGetHrefObj(--ii) if( ii =3D=3D 0 ) ii=3D1 GoToSldNum(ii) } } function GoToFirst(){ GoToSld( GetHrefObj(1).mSldHref ) } function GoToLast() { ii=3DGetSldList().mList.length if( ii !=3D gCurSld ) GoToSld( GetHrefObj(ii).mSldHref ) } function GoToSldNum( num ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue obj =3D GetHrefObj( num ) obj.mVis=3D1 gPrevSld=3DgCurSld gCurSld =3D num; PPTSld.location.replace(MHTMLPrefix+obj.mSldHref) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function GoToSld( href ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue GetHrefObj( GetSldNum(href) ).mVis=3D1 PPTSld.location.replace(MHTMLPrefix+href) } function SldUpdated( id ) { if( id =3D=3D GetHrefObj(gCurSld).mSldHref ) return gPrevSld=3DgCurSld gCurSld=3DGetSldNum(id) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function PrevSldViewed(){ GoToSld( GetHrefObj(gPrevSld).mSldHref ) } function HasPrevSld() { return ( gIsEndShow || ( gCurSld !=3D 1 && GetHrefO= bj( gCurSld-1 ).mVis =3D=3D 1 )||( GetCurSldNum() > 1 ) ) } function HasNextSld() { return (GetCurSldNum() !=3D GetNumSlds()) } function CloseWindow() { if( HideMenu() ) return; var event =3D PPTSld.event; if( !IsFramesMode() && event && (event.keyCode=3D=3D27 || event.keyCode=3D= =3D32 || event.type=3D=3D"click" ) ) window.close( self ); CatchNumKeys( self, event ); } function Unload() { gIsEndShow=3D0; } function SetupEndShow() { gIsEndShow=3D1; PPTSld.document.body.scroll=3D"no"; PPTSld.document.onkeypress=3DCloseWindow; PPTSld.document.onclick=3DCloseWindow; PPTSld.document.oncontextmenu=3D_CM; } function EndShow() { if( IsFramesMode() ) return if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue doc=3DPPTSld.document var dir =3D doc.body.dir if( dir !=3D "rtl" ) dir =3D "ltr"; doc.open() doc.writeln('


' + ENDSHOW_MESG + '

') doc.close() } function SetSldVisited(){ GetSldList().mList[gCurSld-1].mVisited=3Dtrue } function IsSldVisited(){ return GetSldList().mList[gCurSld-1].mVisited } function hrefList( sldHref, visible, advDelay, advClk ) { this.mSldHref=3D this.mNtsHref =3D sldHref this.mOrigVis=3D this.mVis =3D visible this.mVisited=3D false this.mAdvDelay=3D advDelay this.mAdvOnClk=3D advClk } function SldList(arr,curSld,fEnd) { this.mCurSld =3D curSld; this.mList =3D new Array(); var idx =3D 1; for(ii=3D0;ii 0) { PushSldList(sldList,fEnd); gCurSld =3D 1; } else if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue } function PushSldList(arr,fEnd) { var ii =3D gSldStack.length; gSldStack[ii] =3D new SldList(arr,gCurSld,fEnd); GoToSld( gSldStack[ii].mList[0].mSldHref ); } function PopSldList() { if (gSldStack[gSldStack.length-1].fEndShow) EndShow() else { gCurSld =3D gSldStack[gSldStack.length-1].mCurSld; gSldStack[gSldStack.length-1] =3D null; gSldStack.length--; var sldList =3D gSldStack[gSldStack.length-1]; GoToSld( sldList.mList[gCurSld - 1].mSldHref ); } } var custShowList=3Dnew Array(); function ImgBtn( oId,bId,w,action ) { var t=3Dthis t.Perform =3D _IBP t.SetActive =3D _IBSetA t.SetInactive=3D _IBSetI t.SetPressed =3D _IBSetP t.SetDisabled=3D _IBSetD t.Enabled =3D _IBSetE t.ChangeIcon =3D null t.UserAction =3D action t.ChgState =3D _IBUI t.mObjId =3D oId t.mBorderId=3D bId t.mWidth =3D w t.mIsOn =3D t.mCurState =3D 0 } function _IBSetA() { if( this.mIsOn ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _IBSetI() { if( this.mIsOn ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } function _IBSetP() { if( this.mIsOn ) { obj=3Dthis.ChgState( gShadowClr,gHiliteClr,2 ) obj.style.posLeft+=3D1; obj.style.posTop+=3D1 } } function _IBSetD() { obj=3Dthis.ChgState( gFaceClr,gFaceClr,0 ) obj.style.posTop=3D0 } function _IBSetE( state ) { var t=3Dthis GetObj( t.mBorderId ).style.visibility=3D"visible" if( state !=3D t.mIsOn ) { t.mIsOn=3Dstate if( state ) t.SetInactive() else t.SetDisabled() } } function _IBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( t.ChangeIcon ) { obj=3DGetObj(t.mObjId) if( t.ChangeIcon() ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-4)*t.mWidth else obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-0)*t.mWidth } t.SetActive() } } function _IBUI( clr1,clr2,nextState ) { var t=3Dthis SetBorder( GetObj( t.mBorderId ),clr1,clr2 ) obj=3DGetObj( t.mObjId ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-nextState)*t.mWidth-obj= .style.posTop t.mCurState=3DnextState return obj } function TxtBtn( oId,oeId,action,chkState ) { var t=3Dthis t.Perform =3D _TBP t.SetActive =3D _TBSetA t.SetInactive=3D _TBSetI t.SetPressed =3D _TBSetP t.SetDisabled=3D _TBSetD t.SetEnabled =3D _TBSetE t.GetState =3D chkState t.UserAction =3D action t.ChgState =3D _TBUI t.mObjId =3D oId t.m_elementsId=3D oeId t.mIsOn =3D 1 } function _TBSetA() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gHiliteClr,gShadowClr,0,0 ) } function _TBSetI() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) } function _TBSetP() { if( this.mIsOn ) this.ChgState( gShadowClr,gHiliteClr,1,1 ) } function _TBSetD() { this.ChgState( gFaceClr,gFaceClr,0,0 ) this.mIsOn =3D 0 } function _TBSetE() { var t=3Dthis if( !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) else t.ChgState( gShadowClr,gHiliteClr,1,1 ) t.mIsOn =3D 1 } function _TBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( !t.GetState ) return if( t.GetState() ) t.SetPressed() else t.SetActive() } } function _TBUI( clr1,clr2,lOffset,tOffset ) { SetBorder( GetObj( this.mObjId ),clr1,clr2 ) Offset( GetObj( this.m_elementsId ),lOffset,tOffset ) } function Offset( obj, top, left ){ obj.style.top=3Dtop; obj.style.left=3Dle= ft } function SetBorder( obj, upperLeft, lowerRight ) { s=3Dobj.style; s.borderStyle =3D "solid" s.borderWidth =3D 1 s.borderLeftColor =3D s.borderTopColor =3D upperLeft s.borderBottomColor=3D s.borderRightColor =3D lowerRight } function GetBtnObj(){ return gBtnArr[window.event.srcElement.id] } function BtnOnOver(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetActive() } function BtnOnDown(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetPressed() } function BtnOnOut(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetInactive() } function BtnOnUp() { b=3DGetBtnObj() if( b !=3D null ) b.Perform() else Upd() } function GetNtsState(){ return parent.gNtsOpen } function GetOtlState(){ return parent.gOtlOpen } function GetOtlTxtState(){ return parent.gOtlTxtExp } function NtsBtnSetFlag( fVal ) { s=3Ddocument.all.item( this.m_flagId ).style s.display=3D"none" if( fVal ) s.display=3D"" else s.display=3D"none" } function _BSetA_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etActive() } function _BSetI_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etInactive() } function _BSetP_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etPressed() } function _BSetA_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _BSetI_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } var gHiliteClr=3D"THREEDHIGHLIGHT",gShadowClr=3D"THREEDSHADOW",gFaceClr=3D"= THREEDFACE" var gBtnArr =3D new Array() gBtnArr["nb_otl"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOtlPan= e,GetOtlState ) gBtnArr["nb_otlElem"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOt= lPane,GetOtlState ) gBtnArr["nb_nts"] =3D new ImgBtn( "nb_nts","nb_ntsBorder",10,parent.ToggleN= tsPane ) gBtnArr["nb_nts"].SetActive =3D _BSetA_BorderImg; gBtnArr["nb_nts"].SetInactive =3D _BSetI_BorderImg; gBtnArr["nb_ntsBorder"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.= ToggleNtsPane,GetNtsState ) gBtnArr["nb_ntsElem"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.To= ggleNtsPane,GetNtsState ) gBtnArr["nb_prevBorder"] =3D gBtnArr["nb_prev"]=3D new ImgBtn( "nb_prev","n= b_prevBorder",30,parent.GoToPrevSld ) gBtnArr["nb_nextBorder"] =3D gBtnArr["nb_next"]=3D new ImgBtn( "nb_next","n= b_nextBorder",30,parent.GoToNextSld ) gBtnArr["nb_sldshw"]=3D new ImgBtn( "nb_sldshw","nb_sldshwBorder",18,parent= .FullScreen ) gBtnArr["nb_sldshwBorder"] =3D new TxtBtn( "nb_sldshw","nb_sldshwBorder",pa= rent.FullScreen,null ) gBtnArr["nb_sldshwBorder"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwBorder"].SetInactive =3D _BSetI_Border; gBtnArr["nb_sldshwText"] =3D new TxtBtn( "nb_sldshw","nb_sldshwText",parent= .FullScreen,null ) gBtnArr["nb_sldshwText"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwText"].SetInactive =3D _BSetI_Border; gBtnArr["nb_voice"] =3D gBtnArr["nb_voiceBorder"] =3D new ImgBtn( "nb_voice= ","nb_voiceBorder",18,parent.ToggleVNarration ) gBtnArr["nb_otlTxtBorder"] =3D gBtnArr["nb_otlTxt"]=3D new ImgBtn( "nb_otlT= xt","nb_otlTxtBorder",23,parent.ToggleOtlText ) gBtnArr["nb_ntsBorder"].m_flagId=3D "nb_nts" gBtnArr["nb_ntsBorder"].SetFlag =3D NtsBtnSetFlag gBtnArr["nb_otlTxt"].ChangeIcon=3D GetOtlTxtState var sNext=3D"Další",sPrev=3D"Předchozí",sEnd=3D"Kon= ec prezentace",sFont=3D"Arial",sArrow=3D"Šipka",sFreeform=3D"Voln&yacu= te; tvar",sRect=3D"Obdélník",sOval=3D"Ovál" function ShowMenu() { BuildMenu(); var doc=3DPPTSld.document.body,x=3DPPTSld.event.clientX+doc.scrollLeft,y= =3DPPTSld.event.clientY+doc.scrollTop m =3D PPTSld.document.all.item("ctxtmenu") m.style.pixelLeft=3Dx if( (x+m.scrollWidth > doc.clientWidth)&&(x-m.scrollWidth > 0) ) m.style.pixelLeft=3Dx-m.scrollWidth m.style.pixelTop=3Dy if( (y+m.scrollHeight > doc.clientHeight)&&(y-m.scrollHeight > 0) ) m.style.pixelTop=3Dy-m.scrollHeight m.style.display=3D"" } function _CM() { if( !parent.IsFullScrMode() ) return; if(!PPTSld.event.ctrlKey) { ShowMenu() return false } else HideMenu() } function BuildMenu() { if( PPTSld.document.all.item("ctxtmenu") ) return var mObj=3DCreateItem( PPTSld.document.body ) mObj.id=3D"ctxtmenu" mObj.style.visibility=3D"hidden" var s=3DmObj.style s.position=3D"absolute" s.cursor=3D"default" s.width=3D"120px" SetCMBorder(mObj,"menu","black") var iObj=3DCreateItem( mObj ) SetCMBorder( iObj, "threedhighlight","threedshadow" ) iObj.style.padding=3D2 CreateMenuItem( iObj,sNext,M_GoNextSld,M_True ) CreateMenuItem( iObj,sPrev,M_GoPrevSld,M_HasPrevSld ) CreateSeparator( iObj ) CreateMenuItem( iObj,sEnd,M_End,M_True ) mObj.style.visibility=3D"visible" } function Cancel() { window.event.cancelBubble=3Dtrue; window.event.returnVa= lue=3Dfalse } function Highlight() { ChangeClr("activecaption","threedhighlight") } function Deselect() { ChangeClr("threedface","menutext") } function Perform() { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) e.Action() else PPTSld.event.cancelBubble=3Dtrue } function ChangeClr( bg,clr ) { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) { e.style.backgroundColor=3Dbg e.style.color=3Dclr } } function M_HasPrevSld() { return( parent.HasPrevSld() ) } function M_GoNextSld() { if( gIsEndShow ) M_End(); 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 Po= známky
Prezentac= e
Osnova
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